What are the indications and usage for Nucala (mepolizumab) and Dupixent (dupilumab) in patients with severe asthma or atopic dermatitis?

Nucala and Dupixent: Indications and Usage

Dupixent (Dupilumab) - FDA Approved Indications

Dupixent has the broadest indication profile among biologics for type 2 inflammatory diseases, covering eight distinct conditions across dermatologic, respiratory, and immunologic specialties. 1

Primary Indications:

• Atopic Dermatitis: Approved for patients aged ≥6 months with moderate-to-severe disease inadequately controlled by topical therapies or when topical therapies are inadvisable; can be used with or without topical corticosteroids 1

• Asthma: Add-on maintenance treatment for patients aged ≥6 years with moderate-to-severe asthma characterized by eosinophilic phenotype or oral corticosteroid-dependent asthma (not for acute bronchospasm relief) 1

• Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Add-on maintenance treatment for patients aged ≥12 years with inadequately controlled disease 1

• Eosinophilic Esophagitis: Treatment for patients aged ≥1 year weighing at least 15 kg 1

• Prurigo Nodularis: Treatment for adult patients 1

• Chronic Obstructive Pulmonary Disease (COPD): Add-on maintenance for adults with inadequately controlled disease and eosinophilic phenotype (not for acute bronchospasm) 1

• Chronic Spontaneous Urticaria: For patients aged ≥12 years who remain symptomatic despite H1 antihistamine treatment (not for other urticaria forms) 1

• Bullous Pemphigoid: Treatment for adult patients 1

Nucala (Mepolizumab) - FDA Approved Indications

Nucala targets eosinophilic inflammation specifically through IL-5 blockade, with four distinct indications focused on eosinophil-driven diseases. 2

Primary Indications:

• Severe Asthma: Add-on maintenance treatment for patients aged ≥6 years with severe asthma and eosinophilic phenotype (not for acute bronchospasm or status asthmaticus) 2

• Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Add-on maintenance treatment for adults aged ≥18 years with inadequate response to nasal corticosteroids 2

• Eosinophilic Granulomatosis with Polyangiitis (EGPA): Treatment for adult patients 2

• Hypereosinophilic Syndrome (HES): Treatment for patients aged ≥12 years with HES for ≥6 months without identifiable non-hematologic secondary cause 2

Clinical Decision-Making for Biologic Selection

For Chronic Rhinosinusitis with Nasal Polyps:

Dupilumab and omalizumab provide the greatest magnitude of benefit for patient-important outcomes, followed by mepolizumab, based on network meta-analysis data. 3

• Consider dupilumab preferentially for patients with comorbid atopic dermatitis, as it addresses both conditions simultaneously 3
• Consider mepolizumab or benralizumab instead of dupilumab for patients with eosinophilic granulomatosis with polyangiitis (EGPA), as dupilumab may increase peripheral eosinophilia and potentially unmask EGPA 3
• Biologics are conditionally recommended over no biologics for CRSwNP patients who have not sufficiently benefited from intranasal corticosteroids, surgery, or aspirin therapy after desensitization (ATAD) 3

For Atopic Dermatitis:

Dupilumab is the only biologic approved for atopic dermatitis and demonstrates superior efficacy to conventional immunosuppressants with an excellent safety profile over 10 years of follow-up. 3, 1

• Combination therapy with dupilumab and topical corticosteroids delivers EASI 75 (≥75% reduction in severity) in 63-64% of patients at 16 weeks 3
• Real-world data shows pooled EASI 75 of 59% at 16 weeks 3
• Significant improvements occur in itch, quality of life, and sleep parameters 3

For Severe Asthma with Comorbidities:

For patients with severe asthma plus atopic dermatitis, dupilumab is the preferred choice as it targets both conditions through IL-4/IL-13 blockade. 3, 1

• Dupilumab improves both asthma control and dermatologic outcomes in patients with dual pathology 3
• Consider nucala for patients with severe eosinophilic asthma without significant atopic dermatitis 2

Critical Safety Considerations

Dupilumab Ocular Adverse Events:

Ocular surface disorders are the most clinically significant adverse effect of dupilumab, occurring in 6-15% of clinical trial patients and up to 26.1% in real-world practice, but only 4.2% discontinue therapy due to these complications. 3, 4

• Important caveat: Ocular complications occur specifically in atopic dermatitis patients, NOT in patients using dupilumab for asthma, chronic rhinosinusitis, or eosinophilic esophagitis 4
• History of atopic conjunctivitis, keratitis, or pre-existing dry eye disease with keratitis (OR 6.3) are the strongest risk factors 4
• Initiate preservative-free ocular lubricants prophylactically in patients with history of ocular surface disease 3
• Urgent ophthalmology referral within 24 hours is required for: decreased visual acuity, ocular pain, photophobia, or visible corneal damage 4
• Most cases are manageable with topical lubricants and antihistamine eyedrops while continuing dupilumab 4
• For patients requiring topical corticosteroid eyedrops >6 weeks, introduce corticosteroid-sparing therapy 3

Mechanism of Action Differences:

• Dupilumab: Blocks IL-4 receptor alpha subunit, inhibiting both IL-4 and IL-13 signaling—key drivers of type 2 inflammation 3
• Mepolizumab: Anti-IL-5 monoclonal antibody targeting eosinophilic inflammation specifically 2

Dosing Algorithms

Dupilumab Dosing by Indication:

• Atopic Dermatitis (adults/adolescents): 600 mg loading dose, then 300 mg every 2 weeks 1
• Asthma: 400 mg or 600 mg loading dose (based on severity), then 200 mg or 300 mg every 2 weeks 1
• CRSwNP: 300 mg every 2 weeks 1

Nucala Dosing by Indication:

• Severe Asthma (adults/adolescents ≥12 years): 100 mg subcutaneously every 4 weeks 2
• Severe Asthma (children 6-11 years): 40 mg subcutaneously every 4 weeks 2
• CRSwNP: 100 mg subcutaneously every 4 weeks 2
• EGPA/HES: 300 mg (three separate 100-mg injections at least 5 cm apart) every 4 weeks 2